NINDS Alexander Disease Information Page

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What is Alexander Disease?

Alexander disease is one of a group of neurological conditions known as the leukodystrophies, disorders that are the result
of abnormalities in myelin, the “white matter” that protects nerve fibers in the brain. Alexander disease is a progressive
and often fatal disease. The destruction of white matter is accompanied by the formation of Rosenthal fibers, which are abnormal
clumps of protein that accumulate in non-neuronal cells of the brain called astrocytes. Rosenthal fibers are sometimes found
in other disorders, but not in the same amount or area of the brain that are featured in Alexander disease. The infantile
form is the most common type of Alexander disease. It has an onset during the first two years of life. Usually there are
both mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head
size, and seizures. The juvenile form of Alexander disease is less common and has an onset between the ages of two and thirteen.
These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control.
Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple
sclerosis, or may present primarily as a psychiatric disorder. The disease occurs in both males and females, and there are
no ethnic, racial, geographic, or cultural/economic differences in its distribution.

Is there any treatment?

There is no cure for Alexander disease, nor is there a standard course of treatment. Treatment of Alexander disease is symptomatic
and supportive.

What is the prognosis?

The prognosis for individuals with Alexander disease is generally poor. Most children with the infantile form do not survive
past the age of 6. Juvenile and adult onset forms of the disorder have a slower, more lengthy course.

What research is being done?

Recent discoveries show that most individuals (approximately 90 percent) with Alexander disease have a mutation in the gene
that makes glial fibrillary acidic protein (GFAP). GFAP is a normal component of the brain, but it is unclear how the mutations
in this gene causes the disease. In most cases mutations occur spontaneously are not inherited from parents. A small number
of people thought to have Alexander disease do not have identifiable mutations in GFAP, which leads researchers to believe
that there may be other genetic or perhaps even non-genetic causes of Alexander disease. Current research is aimed at understanding
the mechanisms by which the mutations cause disease, developing better animal models for the disorder, and exploring potential
strategies for treatment. At present, there is no exact animal model for the disease; however, mice have been engineered to
produce the same mutant forms of GFAP found in individuals with Alexander disease. These mice form Rosenthal fibers and have
a predisposition for seizures, but do not yet mimic all features of human disease (such as the leukodystrophies). One clinical
study is underway to identify biomarkers of disease severity or progression in samples of blood or cerebrospinal fluid. Such
biomarkers, if found, would be a major advantage for evaluating the response to any treatments that are developed in the future.

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

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